Table_2_The Synergistic Effects of Polysaccharides and Ginsenosides From American Ginseng (Panax quinquefolius L.) Ameliorating Cyclophosphamide-Induced Intestinal Immune Disorders and Gut Barrier Dysfunctions Based on Microbiome-Metabolomics Analysis.xls

Cyclophosphamide (CTX), used in cancer chemotherapy, a high dose of which would cause immunosuppressive effect and intestinal mucosa damage. American ginseng (Panax quinquefolius L.) has a long history of functional food use for immunological disorder, colitis, cancer, and so on. This study aimed to illustrate the underlying mechanism of American ginseng’s immunomodulatory effect in CTX-induced mice. In this study, all groups of American ginseng (American ginseng polysaccharide [AGP], American ginseng ginsenoside [AGG], co-treated with American ginseng polysaccharide and ginsenoside [AGP_AGG]) have relieve the immune disorder by reversing the lymphocyte subsets ratio in spleen and peripheral blood, as well as stimulating CD4+T cells and IgA-secreting cells in small intestine. These three treatment groups, especially AGP_AGG co-treated group recovered the intestine morphology that up-regulated villus height (VH)/crypt depth (CD) ratio, areas of mucins expression, quantity of goblet cells, and expression of tight junction proteins (ZO-1, occludin). Importantly, the microbiome-metabolomics analysis was applied in this study to illustrate the possible immuno-modulating mechanism. The synergistic effect of polysaccharides and ginsenosides (AGP_AGG group) restored the gut microbiota composition and increased various beneficial mucosa-associated bacterial taxa Clostridiales, Bifidobacterium, and Lachnospiraceae, while decreased harmful bacteria Escherichia-Shigella and Peptococcaceae. Also, AGP_AGG group altered various fecal metabolites such as uric acid, xanthurenic acid, acylcarnitine, 9,10-DHOME, 13-HDoHE, LysoPE15:0, LysoPC 16:0, LysoPI 18:0, and so on, that associated with immunometabolism or protective effect of gut barrier. These results suggest AG, particularly co-treated of polysaccharide and ginsenoside may be used as immunostimulants targeting microbiome-metabolomics axis to prevent CTX-induced side effects in cancer patients.

环磷酰胺（Cyclophosphamide, CTX）是癌症化疗中常用药物，高剂量使用可引发免疫抑制与肠黏膜损伤。西洋参（Panax quinquefolius L.）作为功能性食品，在免疫失调、结肠炎、癌症等病症的调理中应用历史悠久。本研究旨在阐明西洋参对环磷酰胺诱导小鼠的免疫调节作用及其潜在机制。
本研究设置了三类西洋参给药方案：西洋参多糖（American ginseng polysaccharide, AGP）组、西洋参皂苷（American ginseng ginsenoside, AGG）组，以及西洋参多糖与皂苷联合给药组（American ginseng polysaccharide and ginsenoside co-treated, AGP_AGG）。结果显示，上述三组均可通过逆转脾脏与外周血中的淋巴细胞亚群比例，同时刺激小肠内CD4+T细胞与分泌免疫球蛋白A（IgA）的细胞，从而缓解免疫紊乱。其中，尤以AGP_AGG联合给药组的效果最为显著，可恢复肠道形态：上调绒毛高度/隐窝深度（villus height/crypt depth, VH/CD）比值、黏蛋白表达区域、杯状细胞数量，以及紧密连接蛋白（ZO-1、occludin）的表达水平。
本研究采用微生物组-代谢组学联合分析方法，阐明了潜在的免疫调节机制。多糖与皂苷的协同作用（AGP_AGG组）可恢复肠道菌群组成，增加多种有益黏膜相关菌属，包括梭菌目（Clostridiales）、双歧杆菌属（Bifidobacterium）、毛螺菌科（Lachnospiraceae），同时减少有害菌属大肠杆菌-志贺氏菌属（Escherichia-Shigella）与消化球菌科（Peptococcaceae）的丰度。此外，AGP_AGG组还可改变多种与免疫代谢或肠道屏障保护功能相关的粪便代谢物，如尿酸、犬尿烯酸、酰基肉碱、9,10-DHOME、13-HDoHE、LysoPE15:0、LysoPC 16:0、LysoPI 18:0等。
上述研究结果表明，西洋参，尤其是多糖与皂苷联合给药的形式，可作为靶向微生物组-代谢组轴的免疫刺激剂，用于预防癌症患者因环磷酰胺治疗引发的不良反应。